Role of the permeability transition pore in cytochrome C release from mitochondria during ischemia-reperfusion in rat liver

Anti-apoptotic and Hepatoprotective Effects of Gomisin A on Fulminant Hepatic Failure Induced by D-Galactosamine and Lipopolysaccharide in Mice

“…The caspase-3 activity was measured using an in vitro fluorogenic peptide substrate, N-acetyl-Asp-Glu-ValAsp-7-amino-4-trifluoromethyl-cumarine (DEVD-AFC; BioMol, Plynouth Meeting, PA, USA), according to the procedure reported by Morin et al (17). Eight hours after the GalN/ LPS treatment, a sample of liver tissue (1 g) was homogenized in 6 ml of a buffer containing 25 mM Tris, 5 mM MgCl 2 , 1 mM EGTA, and 50 µl of a protease inhibitor cocktail (Sigma).…”

Binding mitochondria to cryogel monoliths allows detection of proteins specifically released following permeability transition

“…The dynamics of calciuminduced stimulation of mPT is complex, and it has been suggested that in vivo, mitochondria may release proteins as intracellular calcium levels increase e.g. as a result of injury [6,7]. As the tissue recovers, calcium may be extruded from the cell, and the mPTP reverts to the closed state.…”

“…However the mPTP seemed to be of lesser importance to apoptotic cell death during normal development and to apoptosis regulated by proteins of the Bcl-2 family [13,14]. As shown by Morin et al, cytochrome c release from liver mitochondria occurs independently of mPTP during ischemia, whereas it occurs dependent on mPT in the reperfusion interval [7]. mPT thus has different importance in different settings.…”

“…The principal activator of the mPTP is calcium; the concentration required depends on the surrounding conditions. Mitochondrial permeability transition (mPT) can be induced by increased calcium concentration in vivo [6,7] as well as in vitro [8][9][10][11] and may be reversed by removing calcium [9] or prevented by the administration of inhibitors of mPTP, such as cyclosporin A or its non-immunosuppressive analogues [12]. In the experimental setting, membrane permeabilisation can be achieved by drugs such as the mPTP inducer atractyloside or the ionophore alamethicin.…”

Escherichia coli STb toxin induces apoptosis in intestinal epithelial cell lines

“…The authors revealed that the treatment of hepatocytes with cyclosporin A, an inhibitor of the PTP, prevented the release of proapoptotic proteins such as the cytochrome C and AIF from the mitochondrion, thus inhibiting programmed cell death (Petronilli et al, 2001). A subsequent study also demonstrated the role of PTP in the release of cytochrome C leading to mitochondrion-mediated apoptosis in hepatocytes (Morin et al, 2004). …”